1. Field of the Invention
This invention relates to a hepatic-assist method and apparatus therefor. It relates particularly to a method and apparatus for removing hepatic toxins in cases of acute hepatic failure from human and animal blood. Most particularly, it relates to a novel hepatic-assist method and apparatus which is mechanically simple, portable, sterile and capable of removing virtually all hepatic toxins from human blood without substantial alteration of the blood's pH and electrolyte balance.
2. State of the Art
Various attempts have been made in recent years to remove hepatic toxins from blood by means of chemical sorbents.
One technique described by Juggi in Med. J. Australia, 1:926 (1973) comprises percolation of blood directly through a cation-exchange resin column, the resin being in its mixed sodium, potassium, calcium and magnesium forms. The described method has a number of drawbacks as a hepatic-assist system. Although effective in the removal of ammonium ion, critical hepatic toxins in the middle molecular weight range of 500 to 20,000 and excessive amino acids such as thyrosine and phenylalanine are not removed.
Another method of treating hepatic failure is by hemodialysis with high ultrafiltration rate membranes such as polyacrylonitrile, polycarbonate and anisotropic polysulfone membranes as described by Opolon et al in Trans. Amer. Soc. Artif. Int. 23:701 (1976). In this method, arterial blood from the comatose hepatic patient is connected to a polyacrylonitrile membrane hemodialyzer with a 50 liter closed loop, batch dialysate delivery machine. The dialysate is bicarbonate-based and sterile. Hepatic toxins are dialyzed out of the patient's blood while consequent fluid loss is made up by infused saline solution. Hemodialysis permits rapid removal of hepatic toxins which are extremely diluted in a large volume of dialysate fluid.
The method described by Opolon et al suffers from a number of disadvantages as well. A large volume (50 liters) of dialysate is needed which necessitates water purification systems and special plumbing as well as usage of bulky and expensive dialysate delivery machines. Because of the high volume of dialysate, the amount of body fluid removed cannot be measured accurately, let alone continuously during treatment, which often leads to excess fluid removal which in turn causes severe hypotension, unconsciousness and, in some cases, death. There is a significant loss of essential amino acids and vitamins from the patient due to their substantial dilution in the high volume of dialysate. Finally, the system is cumbersome and does not readily lend itself to bedside treatment.
Still another hepatic-assist method was recently reported by Maini et al in Amer. Soc. Artif. Int. Organs Abstracts, 6; 54 (1977). The reported in vitro technique uses recirculating dialysate comprising banked blood plasma which passes through a large, non-sterile column filled with ground anion-exchange resin, non-ionic resins, and activated carbon woven cloth. For high sorbent efficiency, usage of a finely ground sorbent is preferred by the authors. Bilirubin and bile acids are readily removed by the powdered anion-exchange resin. However, removal of ammonium hepatic toxin is not accomplished. Due to the inherently high pressure drop through a long column filled with considerable amounts of finely ground sorbents, admixed with woven sorbents cloths, the dialysate flow rate is necessarily low. Further, there is a possibility of microemboli formation from tiny sorbents fragments. In order for the treated plasma dialysate to be infused with incoming blood, a sterile column with sterilized sorbents must be used which is impractical with a bulky column and impossible to accomplish by radiation, autoclaving or gas sterilization due to chemical breakdown in the cases of radiation and autoclaving and contamination by adsorption in the case of gas sterilization.